Loading of the ring-shaped Mcm2-7 replicative helicase around DNA licenses eukaryotic origins of replication. During loading, Cdc6, Cdt1, and the origin-recognition complex (ORC) assemble two heterohexameric Mcm2-7 complexes into a head-to-head double hexamer that facilitates bidirectional replication initiation. Using multi-wavelength single-molecule fluorescence to monitor the events of helicase loading, we demonstrate that double-hexamer formation is the result of sequential loading of individual Mcm2-7 complexes. Loading of each Mcm2-7 molecule involves the ordered association and dissociation of distinct Cdc6 and Cdt1 proteins. In contrast, one ORC molecule directs loading of both helicases in each double hexamer. Based on single-molecule FRET, arrival of the second Mcm2-7 results in rapid double-hexamer formation that anticipates Cdc6 and Cdt1 release, suggesting that Mcm-Mcm interactions recruit the second helicase. Our findings reveal the complex protein dynamics that coordinate helicase loading and indicate that distinct mechanisms load the oppositely oriented helicases that are central to bidirectional replication initiation.
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 January 2022.
All research outputs
#6,060,362
of 27,671,578 outputs
Outputs from Cell
#10,546
of 17,831 outputs
Outputs of similar age
#63,447
of 265,202 outputs
Outputs of similar age from Cell
#92
of 122 outputs
Altmetric has tracked 27,671,578 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 17,831 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 61.5. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
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We're also able to compare this research output to 122 others from the same source and published within six weeks on either side of this one. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
